DESCRIPTION: In the Senate Labor, Health and Human Services Appropriations Report, it was recommended that researchers explore issues related to the etiology and natural course of chronic fatigue syndrome using longitudinal, repeated-measures designs, with particular attention to pediatric samples. Researchers have documented the development of a fatigue syndrome following mononucleosis in prospective studies of adults. One objective of the proposed investigation is to prospectively study the relationship between infection with mononucleosis and the onset and course of chronic fatigue syndrome over time in adolescents. The following hypotheses will be tested using a prospective, case-control design: (1) Baseline predictors of post-infectious CFS and fatigue severity at 6 months will include greater levels of baseline psychological distress, having a psychiatric diagnosis at baseline, a greater degree of stressful life events at baseline, and higher levels of activity prior to initial infection; (2) Adolescents with CFS, compared with matched controls, will report higher levels of psychological distress, higher rates of psychiatric diagnoses, a greater degree of stressful life events, and lower levels of physical activity following infection at the 6-, 12-, 24- month time points; and (3) Compared with matched controls, adolescents with CFS will demonstrate lower levels of salivary cortisol (peak and trough), reduced natural killer cell function and count, and elevated proinflammatory cytokines at the 6-, 12-, and 24- month time points. At the 6-month time point (clinic visit), adolescents with CFS will also demonstrate higher rates of orthostatic intolerance; and (4) In response to an exercise challenge test at the six-month time point, compared with matched controls, adolescents with CFS will demonstrate lower levels of salivary cortisol and plasma ACTH, and elevated cytokines - illustrating impaired communication between neuroendocrine and immune systems with physical stress. An exploration of the nature and timing of these relationships would provide a preliminary model of etiology and natural course of illness for adolescents with post-viral chronic fatigue syndrome. Results from this investigation may assist physicians in identifying adolescents at high risk for CFS and allow them to initiate preventative measures.